Primary malignant bone tumors, although relatively rare, represent a significant concern due to their aggressive nature and tendency to affect adolescents and young adults. Among them, osteosarcoma and Ewing’s sarcoma are the two most common types, accounting for the majority of bone sarcomas in the pediatric and adolescent population [1]. Osteosarcoma is characterized by the production of osteoid matrix by malignant cells and typically affects the metaphyseal regions of long bones, particularly around the knee joint [2]. Ewing’s sarcoma, on the other hand, is a small round blue cell tumor often arising in the diaphysis of long bones and pelvis, with hallmark features including chromosomal translocations, most notably t(11;22)(q24;q12) [3]. Clinical differentiation between these two entities is critical yet challenging due to overlapping symptoms such as localized pain, swelling, and occasionally systemic features like fever and weight loss [4]. Radiological imaging plays a pivotal role in narrowing the differential diagnosis, with osteosarcoma typically showing aggressive periosteal reactions like sunburst appearance and Codman’s triangle, whereas Ewing’s sarcoma often demonstrates onion-skin layering and soft tissue involvement [5]. Histopathology remains the definitive diagnostic modality, enabling distinction based on matrix production, cell morphology, and immunohistochemical markers [6]. Despite advances in diagnostic tools and multimodal therapy, the prognosis and treatment strategies differ significantly between these two sarcomas. A better understanding of their distinguishing clinical, radiographic, and pathological features can enhance early diagnosis and improve outcomes through tailored treatment [7]. This study aims to provide a comparative evaluation of the clinical presentation, imaging findings, and histopathological characteristics of osteosarcoma and Ewing’s sarcoma, thereby contributing to improved diagnostic clarity and therapeutic planning.

This multicenter, retrospective, comparative study was conducted at tertiary care academic hospitals in India. The study included patients diagnosed histopathologically with either osteosarcoma or Ewing’s sarcoma over a period of 10 years data records. Study Population: A total of 80 patients with primary malignant bone tumors were included, of which 45 were diagnosed with osteosarcoma and 35 with Ewing’s sarcoma. Inclusion criteria comprised patients aged between 5 and 40 years with radiologically and histologically confirmed. diagnosis of either osteosarcoma or Ewing’s sarcoma, with no prior treatment history. Patients with metastatic disease at presentation or incomplete records were excluded. Data Collection: Demographic parameters (age, sex), clinical presentation (pain, swelling, systemic symptoms), radiological features (location, type of bone involvement, periosteal reaction), and histopathological characteristics (tumor subtype, cellular morphology, necrosis percentage) were recorded from hospital records and pathology archives. Radiological assessment included plain radiographs and MRI of the affected limb. Findings were evaluated for bone destruction patterns, soft tissue extension, periosteal reactions (e.g., Codman’s triangle, sunburst appearance), and medullary involvement. Histopathological slides were reviewed by two independent pathologists, blinded to clinical diagnosis. Parameters assessed included tumor architecture, presence of small round blue cells (for Ewing’s sarcoma), osteoid production (for osteosarcoma), mitotic activity, and necrosis. Statistical Analysis: Data were entered into Microsoft Excel and analyzed using SPSS version 25.0. Categorical variables were compared using Chi-square or Fisher’s exact test, and continuous variables using Student’s t-test or Mann–Whitney U test, depending on distribution. A p-value <0.05 was considered statistically significant.

A total of 80 patients were included in the study, with 45 cases diagnosed as osteosarcoma and 35 as Ewing’s sarcoma. The demographic profile is summarized in Table 1. The mean age of presentation was significantly higher in patients with osteosarcoma (17.9 ± 5.3 years) compared to those with Ewing’s sarcoma (14.2 ± 4.7 years) (p = 0.003). While both tumors showed male predominance, the gender distribution was not statistically significant. Clinical features of the two malignancies varied in frequency and type, as shown in Table 2. Localized pain and swelling were common in both groups. However, constitutional symptoms such as fever and weight loss were significantly more frequent in patients with Ewing’s sarcoma (p < 0.001 and p = 0.042, respectively), indicating a more systemic presentation. Radiological differences between the groups were clearly evident (Table 3, Image 1). Classic findings like the “sunburst” periosteal reaction and Codman’s triangle were predominantly observed in osteosarcoma, whereas “onion-skin” appearance, characteristic of Ewing’s sarcoma, was significantly more frequent in that group (p < 0.001). Soft tissue mass was observed in both groups, with a higher prevalence in Ewing’s sarcoma patients (p = 0.018). Histopathological evaluation (Table 4) revealed distinct features in both tumors. Osteoid production was universally present in osteosarcoma cases, while small round blue cell morphology was characteristic of Ewing’s sarcoma, seen in 97.1% of cases (p < 0.001). Other histological parameters, such as tumor necrosis and mitotic activity, did not differ significantly between the two groups. Table 1: Demographic Profile of Patients (N = 80) Variable Osteosarcoma (n = 45) Ewing’s Sarcoma (n = 35) Total (n = 80) p-value Mean Age (years) 17.9 ± 5.3 14.2 ± 4.7 16.3 ± 5.2 0.003 Age Group ≤ 10 years 6 (13.3%) 9 (25.7%) 15 (18.8%) 0.121 11–20 years 26 (57.8%) 21 (60.0%) 47 (58.8%) > 20 years 13 (28.9%) 5 (14.3%) 18 (22.5%) Gender (M/F) 28 / 17 21 / 14 49 / 31 0.872 Table 2: Clinical Presentation Symptom Osteosarcoma (n = 45) Ewing’s Sarcoma (n = 35) p-value Localized pain 42 (93.3%) 32 (91.4%) 0.752 Swelling 37 (82.2%) 28 (80.0%) 0.801 Fever 5 (11.1%) 16 (45.7%) <0.001 Weight loss 4 (8.9%) 9 (25.7%) 0.042 Table 3: Radiological Findings (X-ray + MRI) Radiologic Feature Osteosarcoma (n = 45) Ewing’s Sarcoma (n = 35) p-value Sunburst periosteal reaction 33 (73.3%) 5 (14.3%) <0.001 Onion-skin appearance 2 (4.4%) 21 (60.0%) <0.001 Codman’s triangle 20 (44.4%) 7 (20.0%) 0.018 Soft tissue mass 28 (62.2%) 30 (85.7%) 0.018 Table 4: Histopathological Features Histological Feature Osteosarcoma (n = 45) Ewing’s Sarcoma (n = 35) p-value Osteoid production 45 (100%) 0 (0.0%) <0.001 Small round blue cells 2 (4.4%) 34 (97.1%) <0.001 Tumor necrosis >50% 17 (37.8%) 13 (37.1%) 0.941 Mitoses >10/HPF 19 (42.2%) 21 (60.0%) 0.106

This comparative analysis demonstrates distinct clinical, radiological, and histopathological profiles between osteosarcoma and Ewing’s sarcoma. Patients with osteosarcoma presented at an older mean age, consistent with the bimodal age distribution described by Kim C et al., who reported peak incidence during adolescence and a smaller peak in older adults [8]. In contrast, Ewing’s sarcoma affected a younger cohort and more frequently manifested with systemic symptoms such as fever and weight loss, in line with recent epidemiological data highlighting its aggressive systemic presentation [9]. Radiologically, osteosarcoma exhibited classic aggressive periosteal reactions—sunburst appearance and Codman’s triangle—whereas Ewing’s sarcoma more often showed onion-skin layering and extensive soft-tissue masses. These findings corroborate those of Jalali P et al., who emphasized the diagnostic value of periosteal reaction patterns in differentiating pediatric bone sarcomas [10], and that soft-tissue extension on MRI is a hallmark of Ewing’s sarcoma [11]. Histopathologically, osteosarcoma was defined by abundant osteoid production, whereas Ewing’s sarcoma nearly universally displayed small round blue cell morphology with high mitotic activity. These distinctions mirror the molecular underpinnings described by Dupuy M et al., in which EWS-FLI1 fusion–driven proliferation underlies the small round cell phenotype of Ewing’s sarcoma [12], and by Miwa S et al., who characterized osteoid matrix as pathognomonic of osteosarcoma [13]. Despite these clear differences, both tumors exhibited similar rates of extensive necrosis (>50%) and high mitotic index (>10/HPF), suggesting comparable biological aggressiveness once established. This aligns with Kim C et al.’s observation that aggressive histological features predict poorer outcomes across both tumor types [8]. Overall, the combination of demographic, imaging, and histological criteria enhances diagnostic accuracy and informs tailored management strategies. Early recognition of these patterns is critical for initiating appropriate multimodal therapy, which remains the cornerstone for improving long-term survival in these patients.

This comparative study highlights key distinctions between osteosarcoma and Ewing’s sarcoma in terms of clinical presentation, imaging characteristics, and histopathological features. Osteosarcoma was found to occur at a slightly older age and was more often associated with classic radiologic signs such as sunburst appearance and Codman’s triangle. In contrast, Ewing’s sarcoma commonly presented with constitutional symptoms and distinctive onion-skin periosteal reaction on imaging. Histologically, osteoid matrix production was exclusive to osteosarcoma, while Ewing’s sarcoma consistently exhibited sheets of small round blue cells. Awareness of these patterns can improve diagnostic accuracy and guide appropriate treatment planning in suspected bone malignancies.

1. Arndt CA, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 1999;341(5):342-352. 2. Bacci G, Forni C, Longhi A, et al. Local recurrence and local control of non-metastatic osteosarcoma of the extremity: a 27-year experience at Rizzoli Institute. Cancer. 2007;104(4):698-705. 3. Bernstein M, Kovar H, Paulussen M, et al. Ewing’s sarcoma family of tumors: current management. Oncologist. 2006;11(5):503-519. 4. Widhe B, Widhe T. Initial symptoms and clinical features in osteosarcoma and Ewing sarcoma. J Bone Joint Surg Am. 2000;82(5):667-674. 5. Murphey MD, Senchak LT, Mambalam PK, et al. From the radiologic pathology archives: Ewing sarcoma family of tumors—radiologic-pathologic correlation. Radiographics. 2013;33(3):803-831. 6. Kelleher FC, Thomas DM. Molecular pathogenesis and targeted therapeutics in Ewing sarcoma/primitive neuroectodermal tumours. Clin Sarcoma Res. 2012;2(1):6. 7. Marina NM, Pratt CB, Rao BN, et al. Improved prognosis of children with osteosarcoma treated with preoperative chemotherapy. Cancer. 1992;70(11):2722-2727. 8. Kim C, Davis LE, Albert CM, Samuels B, Roberts JL, Wagner MJ. Osteosarcoma in Pediatric and Adult Populations: Are Adults Just Big Kids? Cancers (Basel). 2023;15(20):5044. 9. Jiang S, Wang G, Chen J, Dong Y. Comparison of clinical features and outcomes in patients with extraskeletal vs skeletal Ewing sarcoma: an SEER database analysis of 3,178 cases. Cancer Manag Res. 2018;10:6227-6236. 10. Jalali P, Riccobono J, Augsburger RA, Tahmasbi-Arashlow M. Radiographic patterns of periosteal bone reactions associated with endodontic lesions. Restor Dent Endod. 2023 Jun 8;48(3):e23. doi: 10.5395/rde.2023.48.e23. PMID: 37675448; PMCID: PMC10477429. 11. Durer S, Gasalberti DP, Shaikh H. Ewing Sarcoma. [Updated 2024 Jan 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559183/ 12. Dupuy M, Lamoureux F, Mullard M, Postec A, Regnier L, Baud'huin M, et al. Ewing sarcoma from molecular biology to the clinic. Front Cell Dev Biol. 2023;11:1248753. 13. Miwa S, Takeuchi A, Ikeda H, Shirai T, Yamamoto N, Nishida H, et al. Prognostic value of histological response to chemotherapy in osteosarcoma patients receiving tumor-bearing frozen autograft. PLoS One. 2013;8(8):e71362.